The cellular response of rats to Listeria monocytogenes (LM) and other intracellular bacterial parasites would be studied with a view to ascertaining the type(s) of T cells which mediate delayed-type hypersensitivity (DTH) and acquired cellular resistance to infection, the constraints imposed on mediator T cells by determinants coded within the major histocompatibility complex, and factors which regulate the T cell response to infection. The proposed studies would seek to substantiate and extend observations which suggest that cellular resistance to LM is mediated in rats by at least two populations of T cells. Experiments addressed to this problem would be undertaken in genetically defined DPF rats, and would make use of relatively new methods for identifying T cells in this species. Regulation of the T cell response to LM would be analyzed in adoptively immunized subjects. The hypothesis would be tested that suppressor T cells have an immunoregulatory function in infected rats; however, the possbility that other factors are responsible for the unresponsiveness of specifically immunized subjects to a challenge infection with LM would also be investigated. Finally, we would pursue the recent observation that TDL from LM-immune rats can be stimulated in vitro to replicate and generate cells which are cytotoxic for Listeria-antigen-sensitized target cells. Here the focus of research would be on the identity of responder lymphocytes, the MHC constraints, if any, which limit their proliferation and cytotoxic activity, and capacity of in vitro stimulated T cells to operate as mediators of DTH, cellular resistance or suppressors in the intact animal.